EP3506942B1 - Compositions d'agents de liaison et de porteuses pd-l1 pour le traitement de cancers - Google Patents
Compositions d'agents de liaison et de porteuses pd-l1 pour le traitement de cancers Download PDFInfo
- Publication number
- EP3506942B1 EP3506942B1 EP17778387.5A EP17778387A EP3506942B1 EP 3506942 B1 EP3506942 B1 EP 3506942B1 EP 17778387 A EP17778387 A EP 17778387A EP 3506942 B1 EP3506942 B1 EP 3506942B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- binding
- nanoparticle composition
- immunotherapy
- nanoparticle
- nanoparticles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000011230 binding agent Substances 0.000 title claims description 216
- 239000000203 mixture Substances 0.000 title claims description 212
- 206010028980 Neoplasm Diseases 0.000 title claims description 111
- 239000002105 nanoparticle Substances 0.000 claims description 407
- 238000009169 immunotherapy Methods 0.000 claims description 145
- 239000003814 drug Substances 0.000 claims description 90
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 78
- 102000014914 Carrier Proteins Human genes 0.000 claims description 73
- 108010078791 Carrier Proteins Proteins 0.000 claims description 73
- 229940124597 therapeutic agent Drugs 0.000 claims description 73
- 238000000034 method Methods 0.000 claims description 62
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 47
- 229960003852 atezolizumab Drugs 0.000 claims description 40
- 201000011510 cancer Diseases 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 35
- 108020001507 fusion proteins Proteins 0.000 claims description 30
- 102000037865 fusion proteins Human genes 0.000 claims description 30
- 108091023037 Aptamer Proteins 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 102000009027 Albumins Human genes 0.000 claims description 20
- 108010088751 Albumins Proteins 0.000 claims description 20
- 229960001592 paclitaxel Drugs 0.000 claims description 19
- 229930012538 Paclitaxel Natural products 0.000 claims description 18
- 229960000106 biosimilars Drugs 0.000 claims description 15
- 239000000427 antigen Substances 0.000 claims description 14
- 108091007433 antigens Proteins 0.000 claims description 14
- 102000036639 antigens Human genes 0.000 claims description 14
- -1 triplatin Chemical compound 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 11
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 10
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 10
- 229960002411 imatinib Drugs 0.000 claims description 10
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 10
- 229960003301 nivolumab Drugs 0.000 claims description 9
- 229960002621 pembrolizumab Drugs 0.000 claims description 8
- 229960004316 cisplatin Drugs 0.000 claims description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 7
- 229950010773 pidilizumab Drugs 0.000 claims description 6
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 5
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 5
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 5
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 claims description 5
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 5
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 5
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 5
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 5
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 5
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 5
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 5
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 5
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 5
- 239000002067 L01XE06 - Dasatinib Substances 0.000 claims description 5
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 5
- 239000005536 L01XE08 - Nilotinib Substances 0.000 claims description 5
- 239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 5
- 108010000817 Leuprolide Proteins 0.000 claims description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 5
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 5
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 claims description 5
- 229960000853 abiraterone Drugs 0.000 claims description 5
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 claims description 5
- 229960002707 bendamustine Drugs 0.000 claims description 5
- 229960001467 bortezomib Drugs 0.000 claims description 5
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 5
- 229960001573 cabazitaxel Drugs 0.000 claims description 5
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 claims description 5
- 229960004562 carboplatin Drugs 0.000 claims description 5
- 190000008236 carboplatin Chemical compound 0.000 claims description 5
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 5
- 229960004630 chlorambucil Drugs 0.000 claims description 5
- 229960004397 cyclophosphamide Drugs 0.000 claims description 5
- 229960002448 dasatinib Drugs 0.000 claims description 5
- 229960003668 docetaxel Drugs 0.000 claims description 5
- 229960004679 doxorubicin Drugs 0.000 claims description 5
- 229960001904 epirubicin Drugs 0.000 claims description 5
- 229960001433 erlotinib Drugs 0.000 claims description 5
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 5
- 229960005420 etoposide Drugs 0.000 claims description 5
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 5
- 229960005167 everolimus Drugs 0.000 claims description 5
- 239000012634 fragment Substances 0.000 claims description 5
- 229960002584 gefitinib Drugs 0.000 claims description 5
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 5
- 229960000908 idarubicin Drugs 0.000 claims description 5
- 229960004891 lapatinib Drugs 0.000 claims description 5
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 5
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims description 5
- 229960004338 leuprorelin Drugs 0.000 claims description 5
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 5
- 229960001924 melphalan Drugs 0.000 claims description 5
- 229960000485 methotrexate Drugs 0.000 claims description 5
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 5
- 229960001156 mitoxantrone Drugs 0.000 claims description 5
- 229950007221 nedaplatin Drugs 0.000 claims description 5
- 229960001346 nilotinib Drugs 0.000 claims description 5
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims description 5
- 229960001756 oxaliplatin Drugs 0.000 claims description 5
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 5
- 229960000639 pazopanib Drugs 0.000 claims description 5
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 5
- 229960005079 pemetrexed Drugs 0.000 claims description 5
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims description 5
- IIMIOEBMYPRQGU-UHFFFAOYSA-L picoplatin Chemical compound N.[Cl-].[Cl-].[Pt+2].CC1=CC=CC=N1 IIMIOEBMYPRQGU-UHFFFAOYSA-L 0.000 claims description 5
- 229950005566 picoplatin Drugs 0.000 claims description 5
- 229960003452 romidepsin Drugs 0.000 claims description 5
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 claims description 5
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 claims description 5
- 108010091666 romidepsin Proteins 0.000 claims description 5
- 229960005399 satraplatin Drugs 0.000 claims description 5
- 190014017285 satraplatin Chemical compound 0.000 claims description 5
- 229960003787 sorafenib Drugs 0.000 claims description 5
- 229960001796 sunitinib Drugs 0.000 claims description 5
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims description 5
- 229960001278 teniposide Drugs 0.000 claims description 5
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 5
- 229960003862 vemurafenib Drugs 0.000 claims description 5
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 claims description 5
- 229960003048 vinblastine Drugs 0.000 claims description 5
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 5
- 229960004528 vincristine Drugs 0.000 claims description 5
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 5
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 5
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 5
- 229960002066 vinorelbine Drugs 0.000 claims description 5
- 229950007213 spartalizumab Drugs 0.000 claims description 4
- 102000008096 B7-H1 Antigen Human genes 0.000 claims 6
- 229940050528 albumin Drugs 0.000 claims 2
- 190000005734 nedaplatin Chemical compound 0.000 claims 2
- 239000002245 particle Substances 0.000 description 90
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 76
- 229940028652 abraxane Drugs 0.000 description 68
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 67
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 64
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 62
- 210000004027 cell Anatomy 0.000 description 42
- 230000001225 therapeutic effect Effects 0.000 description 41
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 39
- 235000018102 proteins Nutrition 0.000 description 31
- 102000004169 proteins and genes Human genes 0.000 description 31
- 108090000623 proteins and genes Proteins 0.000 description 31
- 239000000243 solution Substances 0.000 description 26
- 229940045513 CTLA4 antagonist Drugs 0.000 description 22
- 238000002347 injection Methods 0.000 description 21
- 239000007924 injection Substances 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 229940079593 drug Drugs 0.000 description 16
- 238000004108 freeze drying Methods 0.000 description 16
- 230000001965 increasing effect Effects 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 238000001990 intravenous administration Methods 0.000 description 15
- 239000000546 pharmaceutical excipient Substances 0.000 description 15
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 14
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 201000001441 melanoma Diseases 0.000 description 13
- 238000009472 formulation Methods 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 12
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 10
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 229960004641 rituximab Drugs 0.000 description 10
- 238000012384 transportation and delivery Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 206010025323 Lymphomas Diseases 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 230000002195 synergetic effect Effects 0.000 description 7
- 230000037361 pathway Effects 0.000 description 6
- 230000010412 perfusion Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 108091006905 Human Serum Albumin Proteins 0.000 description 5
- 102000008100 Human Serum Albumin Human genes 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 5
- 229950002916 avelumab Drugs 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 239000004067 bulking agent Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 238000012377 drug delivery Methods 0.000 description 5
- 229950009791 durvalumab Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 206010005003 Bladder cancer Diseases 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 208000006265 Renal cell carcinoma Diseases 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229960000397 bevacizumab Drugs 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 229960005386 ipilimumab Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 201000005112 urinary bladder cancer Diseases 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 3
- 101001117312 Homo sapiens Programmed cell death 1 ligand 2 Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 229940049595 antibody-drug conjugate Drugs 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000007541 cellular toxicity Effects 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 208000006332 Choriocarcinoma Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 101710094000 Programmed cell death 1 ligand 1 Proteins 0.000 description 2
- 241000508269 Psidium Species 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 201000010208 Seminoma Diseases 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- 101150071882 US17 gene Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000012575 bio-layer interferometry Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000012830 cancer therapeutic Substances 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 239000002577 cryoprotective agent Substances 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000006240 deamidation Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000294 dose-dependent toxicity Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002767 hepatic artery Anatomy 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000008443 lung non-squamous non-small cell carcinoma Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000000066 myeloid cell Anatomy 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 238000006384 oligomerization reaction Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229940066453 tecentriq Drugs 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 231100000167 toxic agent Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 230000036326 tumor accumulation Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 108010058566 130-nm albumin-bound paclitaxel Proteins 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- CDEURGJCGCHYFH-DJLDLDEBSA-N 5-ethynyl-2'-deoxyuridine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C#C)=C1 CDEURGJCGCHYFH-DJLDLDEBSA-N 0.000 description 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 1
- 206010001413 Adult T-cell lymphoma/leukaemia Diseases 0.000 description 1
- 239000012118 Alexa Fluor 750 Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000013165 Bowen disease Diseases 0.000 description 1
- 208000019337 Bowen disease of the skin Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 230000005653 Brownian motion process Effects 0.000 description 1
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 108010061711 Gliadin Proteins 0.000 description 1
- 229940121672 Glycosylation inhibitor Drugs 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 1
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 1
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 101710094902 Legumin Proteins 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108010079855 Peptide Aptamers Proteins 0.000 description 1
- 102100036154 Platelet basic protein Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 108010055615 Zein Proteins 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000007068 beta-elimination reaction Methods 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 238000005537 brownian motion Methods 0.000 description 1
- 230000005880 cancer cell killing Effects 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 231100001157 chemotherapeutic toxicity Toxicity 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000000562 conjugate Substances 0.000 description 1
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 208000028919 diffuse intrinsic pontine glioma Diseases 0.000 description 1
- 208000026144 diffuse midline glioma, H3 K27M-mutant Diseases 0.000 description 1
- NEKNNCABDXGBEN-UHFFFAOYSA-L disodium;4-(4-chloro-2-methylphenoxy)butanoate;4-(2,4-dichlorophenoxy)butanoate Chemical compound [Na+].[Na+].CC1=CC(Cl)=CC=C1OCCCC([O-])=O.[O-]C(=O)CCCOC1=CC=C(Cl)C=C1Cl NEKNNCABDXGBEN-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 102000048776 human CD274 Human genes 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000005746 immune checkpoint blockade Effects 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 229940092110 macugen Drugs 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 229940127285 new chemical entity Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 108091008104 nucleic acid aptamers Proteins 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000010110 radioembolization Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 208000030829 thyroid gland adenocarcinoma Diseases 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 239000008181 tonicity modifier Substances 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 208000023747 urothelial carcinoma Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
- 229940055760 yervoy Drugs 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Claims (13)
- Composition de nanoparticules pour une utilisation dans le traitement d'un cancer qui exprime le PD-L1dans laquelle chacune des nanoparticules comprend de l'albumine, de l'atézolizumab, et du paclitaxel, dans laquelle les nanoparticules sont capables de se lier au PD-L1 ; etdans laquelle la composition de nanoparticules est destinée à une administration avec une immunothérapie anti-PD-1.
- Immunothérapie anti-PD-1 pour une utilisation dans le traitement d'un cancer qui exprime le PD-L1,dans laquelle l'immunothérapie anti-PD-1 est destinée à une administration avec une composition de nanoparticules ; etdans laquelle la composition de nanoparticules comprend une ou plusieurs nanoparticules comprenant de l'albumine, de l'atézolizumab, et du paclitaxel, dans laquelle les nanoparticules sont capables de se lier au PD-L1.
- Composition de nanoparticules pour une utilisation selon la revendication 1 ou immunothérapie anti-PD-1 pour une utilisation selon la revendication 2, dans laquelle l'immunothérapie anti-PD-1 comprend un agent de liaison capable de se lier au PD-1, dans laquelle l'agent de liaison est un anticorps, un fragment de celui-ci se liant à un antigène, un aptamère, une protéine de fusion, ou toute combinaison de ceux-ci.
- Composition de nanoparticules ou immunothérapie anti-PD-1 pour une utilisation selon la revendication 3, dans laquellel'agent de liaison est un agent de liaison libre ; oul'agent de liaison est une protéine de fusion et facultativement dans laquelle la protéine de fusion est AMP-224 ou AMP-514.
- Composition de nanoparticules ou immunothérapie anti-PD-1 pour une utilisation selon la revendication 3, dans laquelle l'agent de liaison est intégré sur et/ou dans une nanoparticule comprenant une protéine porteuse et ledit agent de liaison, et facultativement un second agent thérapeutique.
- Composition de nanoparticules ou immunothérapie anti-PD-1 pour une utilisation selon la revendication 3, dans laquelle l'agent de liaison est un anticorps anti-PD-1, facultativement dans laquelle l'anticorps anti-PD-1 est le nivolumab, le pembrolizumab, le pidilizumab, le PDR001, ou un agent biosimilaire de ceux-ci.
- Composition de nanoparticules ou immunothérapie anti-PD-1 pour une utilisation selon l'une quelconque des revendications 1 à 6, dans laquelle la composition de nanoparticules est lyophilisée, le procédé comprenant en outre l'étape consistant à reconstituer la composition de nanoparticules dans une solution aqueuse avant l'administration.
- Composition de nanoparticules ou immunothérapie anti-PD-1 pour une utilisation selon l'une quelconque des revendications 3 à 6, dans laquelle la composition de nanoparticules et l'agent de liaison sont destinés à une administration simultanée ou séquentielle, facultativement dans laquelle la composition de nanoparticules est destinée à une administration avant l'administration de l'agent de liaison ou dans laquelle l'agent de liaison est destiné à une administration avant l'administration de la composition de nanoparticules.
- Composition de nanoparticules ou immunothérapie anti-PD-1 pour une utilisation selon l'une quelconque des revendications 1 à 8, comprenant en outre un agent thérapeutique supplémentaire sélectionné parmi l'abiratérone, la bendamustine, le bortézomib, le carboplatine, le cabazitaxel, le cisplatine, le chlorambucil, le dasatinib, le docétaxel, la doxorubicine, l'épirubicine, l'erlotinib, l'étoposide, l'évérolimus, le géfitinib, l'idarubicine, l'imatinib, l'hydroxyurée, l'imatinib, le lapatinib, la leuproréline, le melphalan, le méthotrexate, la mitoxantrone, le nédaplatine, le nilotinib, l'oxaliplatine, le pazopanib, le pémétrexed, le picoplatine, la romidepsine, le satraplatine, le sorafénib, le vemurafenib, le sunitinib, le téniposide, le triplatine, la vinblastine, la vinorelbine, la vincristine, ou le cyclophosphamide.
- Nanoparticule comprenant :(a) de l'albumine,(b) de l'atézolizumab, et(c) du paclitaxel,de sorte que ladite nanoparticule est capable de se lier au PD-L1.
- Composition de nanoparticules comprenant la nanoparticule selon la revendication 10, facultativement qui est lyophilisée, dans laquelle, lors de la reconstitution avec une solution aqueuse, la nanoparticule est capable de se lier au PD-L1.
- Composition de nanoparticules selon la revendication 11, comprenant en outre un agent thérapeutique supplémentaire sélectionné parmi l'abiratérone, la bendamustine, le bortézomib, le carboplatine, le cabazitaxel, le cisplatine, le chlorambucil, le dasatinib, le docétaxel, la doxorubicine, l'épirubicine, l'erlotinib, l'étoposide, l'évérolimus, le géfitinib, l'idarubicine, l'imatinib, l'hydroxyurée, l'imatinib, le lapatinib, la leuproréline, le melphalan, le méthotrexate, la mitoxantrone, le nédaplatine, le nilotinib, l'oxaliplatine, le pazopanib, le pémétrexed, le picoplatine, la romidepsine, le satraplatine, le sorafénib, le vemurafenib, le sunitinib, le téniposide, le triplatine, la vinblastine, la vinorelbine, la vincristine, ou le cyclophosphamide.
- Kit comprenant la composition de nanoparticules selon la revendication 12 et un agent d'immunothérapie anti-PD-1 qui est un anticorps, un fragment de celui-ci se liant à un antigène, un aptamère, une protéine de fusion, ou toute combinaison de ceux-ci, capable de se lier au PD-1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP22206923.9A EP4177271A1 (fr) | 2016-09-01 | 2017-08-31 | Compositions d'agent de liaison de support-pd-l1 pour le traitement de cancers |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662382731P | 2016-09-01 | 2016-09-01 | |
| PCT/US2017/049746 WO2018045239A1 (fr) | 2016-09-01 | 2017-08-31 | Compositions d'agents de liaison et de porteuses pd-l1 pour le traitement de cancers |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP22206923.9A Division EP4177271A1 (fr) | 2016-09-01 | 2017-08-31 | Compositions d'agent de liaison de support-pd-l1 pour le traitement de cancers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP3506942A1 EP3506942A1 (fr) | 2019-07-10 |
| EP3506942B1 true EP3506942B1 (fr) | 2022-11-16 |
Family
ID=60009705
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP17778387.5A Active EP3506942B1 (fr) | 2016-09-01 | 2017-08-31 | Compositions d'agents de liaison et de porteuses pd-l1 pour le traitement de cancers |
| EP22206923.9A Pending EP4177271A1 (fr) | 2016-09-01 | 2017-08-31 | Compositions d'agent de liaison de support-pd-l1 pour le traitement de cancers |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP22206923.9A Pending EP4177271A1 (fr) | 2016-09-01 | 2017-08-31 | Compositions d'agent de liaison de support-pd-l1 pour le traitement de cancers |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US11548946B2 (fr) |
| EP (2) | EP3506942B1 (fr) |
| JP (2) | JP2019526578A (fr) |
| KR (2) | KR20220151022A (fr) |
| CN (1) | CN109890419A (fr) |
| AU (1) | AU2017318668A1 (fr) |
| CA (1) | CA3035378A1 (fr) |
| ES (1) | ES2937291T3 (fr) |
| MX (1) | MX2019002474A (fr) |
| RU (1) | RU2019109211A (fr) |
| WO (1) | WO2018045239A1 (fr) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT2707030T (pt) | 2011-05-09 | 2020-05-22 | Mayo Found Medical Education & Res | Tratamentos de cancro |
| CA2917407C (fr) | 2012-10-01 | 2023-03-14 | Mayo Foundation For Medical Education And Research | Complexes de nanoparticules d'anticorps-albumine pour le traitement du cancer |
| US10213513B2 (en) | 2014-06-16 | 2019-02-26 | Mayo Foundation For Medical Education And Research | Treating myelomas |
| US9446148B2 (en) | 2014-10-06 | 2016-09-20 | Mayo Foundation For Medical Education And Research | Carrier-antibody compositions and methods of making and using the same |
| CN107683131B (zh) | 2015-06-04 | 2021-09-28 | 克里蒂泰克公司 | 紫杉烷颗粒及其用途 |
| TW201707725A (zh) | 2015-08-18 | 2017-03-01 | 美國馬友醫藥教育研究基金會 | 載體－抗體組合物及其製造及使用方法 |
| TW201713360A (en) | 2015-10-06 | 2017-04-16 | Mayo Foundation | Methods of treating cancer using compositions of antibodies and carrier proteins |
| EP3399861A4 (fr) | 2016-01-07 | 2019-08-07 | Mayo Foundation for Medical Education and Research | Procédés de traitement du cancer par interféron |
| EP3413874A4 (fr) | 2016-02-12 | 2020-01-22 | Mayo Foundation for Medical Education and Research | Traitements des cancers hématologiques |
| AU2017238118A1 (en) | 2016-03-21 | 2018-10-11 | Mayo Foundation For Medical Education And Research | Methods for improving the therapeutic index for a chemotherapeutic drug |
| US11305020B2 (en) | 2016-03-21 | 2022-04-19 | Mayo Foundation For Medical Education And Research | Methods for reducing toxicity of a chemotherapeutic drug |
| AU2017246316B2 (en) | 2016-04-04 | 2022-09-29 | Crititech, Inc. | Methods for solid tumor treatment |
| US10618969B2 (en) | 2016-04-06 | 2020-04-14 | Mayo Foundation For Medical Education And Research | Carrier-binding agent compositions and methods of making and using the same |
| RU2019109209A (ru) | 2016-09-01 | 2020-10-05 | Мэйо Фаундейшн Фор Медикал Эдьюкейшн Энд Рисерч | Способ и композиции для направленного на мишень воздействия при лечении т-клеточных видов рака |
| KR20220151022A (ko) | 2016-09-01 | 2022-11-11 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | 암 치료용 담체－ｐｄ－ｌ１ 결합제 조성물 |
| US11590098B2 (en) | 2016-09-06 | 2023-02-28 | Mayo Foundation For Medical Education And Research | Methods of treating triple-negative breast cancer using compositions of antibodies and carrier proteins |
| KR20230011473A (ko) | 2016-09-06 | 2023-01-20 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | Ｐｄ－ｌ１ 발현 암의 치료 방법 |
| US11311631B2 (en) | 2016-09-06 | 2022-04-26 | Mayo Foundation For Medical Education And Research | Paclitaxel-albumin-binding agent compositions and methods for using and making the same |
| US11040027B2 (en) | 2017-01-17 | 2021-06-22 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
| WO2018195416A1 (fr) | 2017-04-21 | 2018-10-25 | Mayo Foundation For Medical Education And Research | Complexes polypeptide-anticorps et leurs utilisations |
| KR20200014279A (ko) | 2017-06-09 | 2020-02-10 | 크리티테크, 인크. | 항신생물 입자의 낭내 주사에 의한 상피낭종의 치료 |
| BR112019022720A2 (pt) | 2017-06-14 | 2020-05-12 | Crititech, Inc. | Métodos para tratar distúrbios pulmonares |
| RU2020110399A (ru) | 2017-10-03 | 2021-11-09 | Крититек, Инк. | Местная доставка противоопухолевых частиц в комбинации с системной доставкой иммунотерапевтических агентов для лечения рака |
| US20210023233A1 (en) * | 2018-02-06 | 2021-01-28 | Mayo Foundation For Medical Education And Research | Antibody-peptide complexes and uses thereof |
| CN109512798B (zh) * | 2019-01-15 | 2022-05-13 | 南京从一医药科技有限公司 | 一种用于抗肿瘤免疫治疗的药物组合物纳米体系 |
| CN110623942B (zh) * | 2019-09-30 | 2020-09-22 | 武汉大学 | 一种全反式维甲酸纳米药物制剂、其制备方法及应用 |
| WO2021143767A1 (fr) * | 2020-01-15 | 2021-07-22 | 信达生物制药(苏州)有限公司 | Préparation d'anticorps bispécifique combinant pd-1 et pd-l1 et son utilisation |
Family Cites Families (124)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4350687A (en) | 1980-02-10 | 1982-09-21 | Research Corporation | Platelet derived cell growth factor |
| JPS60146833A (ja) | 1984-01-10 | 1985-08-02 | Green Cross Corp:The | モノクロ−ナル抗体製剤 |
| JPS6178731A (ja) | 1985-05-20 | 1986-04-22 | Green Cross Corp:The | 加熱処理免疫グロブリン製剤 |
| CA1327161C (fr) | 1987-09-01 | 1994-02-22 | Mitsugu Kobayashi | Composition pharmaceutique lyophilisee d'un derive de neocarzinostatine |
| SE8801537D0 (sv) | 1988-04-26 | 1988-04-26 | Ellco Food Ab | Cellodlingsmedium samt forfarande for dess framstellning |
| US5252713A (en) | 1988-09-23 | 1993-10-12 | Neorx Corporation | Polymeric carriers for non-covalent drug conjugation |
| CA2049342A1 (fr) | 1989-03-27 | 1990-09-28 | Sally Bolmer | Formules pour stabiliser les anticorps igm |
| US5116944A (en) | 1989-12-29 | 1992-05-26 | Neorx Corporation | Conjugates having improved characteristics for in vivo administration |
| US5216130A (en) | 1990-05-17 | 1993-06-01 | Albany Medical College | Complex for in-vivo target localization |
| US5270163A (en) | 1990-06-11 | 1993-12-14 | University Research Corporation | Methods for identifying nucleic acid ligands |
| US6011020A (en) | 1990-06-11 | 2000-01-04 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand complexes |
| US6147204A (en) | 1990-06-11 | 2000-11-14 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand complexes |
| EP1493825A3 (fr) | 1990-06-11 | 2005-02-09 | Gilead Sciences, Inc. | Procédé pour la production de ligands constitués par des acides nucléiques |
| US5840867A (en) | 1991-02-21 | 1998-11-24 | Gilead Sciences, Inc. | Aptamer analogs specific for biomolecules |
| WO1994004679A1 (fr) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Procede pour fabriquer des anticorps humanises |
| US5582981A (en) | 1991-08-14 | 1996-12-10 | Gilead Sciences, Inc. | Method for identifying an oligonucleotide aptamer specific for a target |
| US5260308A (en) | 1991-11-06 | 1993-11-09 | Mayo Foundation For Medical Education And Research | Method to increase permeability of the blood-nerve/brain barriers to proteins |
| US5736137A (en) | 1992-11-13 | 1998-04-07 | Idec Pharmaceuticals Corporation | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
| WO1999000113A1 (fr) | 1997-06-27 | 1999-01-07 | Vivorx Pharmaceuticals, Inc. | Nouvelles formulations d'agents pharmacologiques, leurs procedes de preparation et d'utilisation |
| US6537579B1 (en) | 1993-02-22 | 2003-03-25 | American Bioscience, Inc. | Compositions and methods for administration of pharmacologically active compounds |
| US6699843B2 (en) | 1995-06-07 | 2004-03-02 | Gilead Sciences, Inc. | Method for treatment of tumors using nucleic acid ligands to PDGF |
| DE69722793T2 (de) | 1996-04-26 | 2004-05-19 | Genaera Corp. | Squalamin in kombination mit anderen antikrebs-mittelen zur behandlung von tumoren |
| GB9613182D0 (en) | 1996-06-24 | 1996-08-28 | Nycomed Imaging As | Method |
| US5728541A (en) | 1996-07-12 | 1998-03-17 | Precision Therapeutics, Inc. | Method for preparing cell cultures from biologial specimens for chemotherapeutic and other assays |
| US6416967B2 (en) | 1996-07-12 | 2002-07-09 | Precision Therapeutics, Inc. | Method of using multicellular particulates to analyze malignant or hyperproliferative tissue |
| US6051698A (en) | 1997-06-06 | 2000-04-18 | Janjic; Nebojsa | Vascular endothelial growth factor (VEGF) nucleic acid ligand complexes |
| US8853260B2 (en) | 1997-06-27 | 2014-10-07 | Abraxis Bioscience, Llc | Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof |
| US7041301B1 (en) | 1997-11-07 | 2006-05-09 | Mayo Foundation For Medical Education And Research | Interferon immunotherapy |
| US6616925B1 (en) | 1998-04-02 | 2003-09-09 | I.D.M. Immuno-Designed Molecules | Combined preparation for the treatment of neoplasic diseases or of infectious diseases |
| US6180348B1 (en) | 1998-04-20 | 2001-01-30 | Weihua Li | Method of isolating target specific oligonucleotide ligands |
| US7112409B2 (en) | 1999-01-29 | 2006-09-26 | Center For Molecular Medicine And Immunology | Method of determining cytokine dosage for myelosuppressive state |
| US7534866B2 (en) | 2005-10-19 | 2009-05-19 | Ibc Pharmaceuticals, Inc. | Methods and compositions for generating bioactive assemblies of increased complexity and uses |
| JP2001072589A (ja) | 1999-07-06 | 2001-03-21 | Toagosei Co Ltd | 制癌剤 |
| US6420378B1 (en) | 1999-10-15 | 2002-07-16 | Supergen, Inc. | Inhibition of abnormal cell proliferation with camptothecin and combinations including the same |
| DE10132502A1 (de) | 2001-07-05 | 2003-01-23 | Gsf Forschungszentrum Umwelt | Angriff auf Tumorzellen mit fehlender, niedriger oder anormaler MHC-Expression durch kombinieren von nicht MHC-Restringierten T-Zellen/NK-Zellen und MHC-Restringierten Zellen |
| CN1652820A (zh) | 2002-04-12 | 2005-08-10 | 梅达雷克斯公司 | 使用ctla－4抗体的治疗方法 |
| WO2004004658A2 (fr) | 2002-07-09 | 2004-01-15 | Point Therapeutics, Inc. | Procedes et compositions ayant trait a des composes d'isoleucine boroproline |
| EP1539234A4 (fr) | 2002-09-05 | 2006-02-15 | Medimmune Inc | Methodes de prevention ou de traitement de malignites cellulaires par administration d'antagonistes de cd2 |
| EP1545204B1 (fr) | 2002-09-06 | 2016-08-10 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Immunotherapie utilisant des lymphocytes specifiques d'un antigene selectionnes in vitro apres une chimiotherapie non myeloablative appauvrissant les lymphocytes |
| EP3470084A1 (fr) | 2002-12-09 | 2019-04-17 | Abraxis BioScience, LLC | Compositions comprenant des nanoparticules d'albumine et méthodes pour la libération de principes actifs |
| US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| AR046510A1 (es) | 2003-07-25 | 2005-12-14 | Regeneron Pharma | Composicion de un antagonista de vegf y un agente anti-proliferativo |
| WO2005039492A2 (fr) | 2003-10-22 | 2005-05-06 | The John Hopkins University | Therapie bacteriolytique combinee amelioree pour le traitement de tumeurs |
| ATE538800T1 (de) | 2004-04-22 | 2012-01-15 | Lilly Co Eli | Kombinationstherapie zur krebsbehandlung |
| WO2006034455A2 (fr) | 2004-09-23 | 2006-03-30 | Vasgene Therapeutics, Inc. | Composes de polypeptides pour l'inhibition de l'angiogenese et de croissance tumorale |
| US20090004118A1 (en) | 2004-10-07 | 2009-01-01 | Shuming Nie | Multifunctional Nanoparticle Conjugates And Their Use |
| KR101914254B1 (ko) | 2005-02-18 | 2018-11-02 | 아브락시스 바이오사이언스, 엘엘씨 | 치료제의 조합 및 투여 방식, 및 조합 요법 |
| US8735394B2 (en) | 2005-02-18 | 2014-05-27 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
| US20070166388A1 (en) | 2005-02-18 | 2007-07-19 | Desai Neil P | Combinations and modes of administration of therapeutic agents and combination therapy |
| CN103285392A (zh) | 2005-04-26 | 2013-09-11 | 卫材R&D管理株式会社 | 用于癌症免疫疗法的组合物和其用途 |
| US10183076B2 (en) | 2005-05-16 | 2019-01-22 | Resdevco Research And Development Co. L | Topical compositions for treatment of irritation of mucous membranes |
| PT3311805T (pt) | 2005-08-31 | 2020-04-21 | Abraxis Bioscience Llc | Composições compreendendo agentes farmacêuticos pouco hidrossolúveis e agentes antimicrobianos |
| CN101291658B (zh) | 2005-08-31 | 2014-04-16 | 阿布拉科斯生物科学有限公司 | 用于制备稳定性增加的水难溶性药物的组合物和方法 |
| US7776832B2 (en) | 2006-04-21 | 2010-08-17 | Gem Pharmaceuticals, Llc | Anticancer treatment with a combination of taxanes and 13-deoxyanthracyclines |
| CA2664740C (fr) | 2006-09-26 | 2021-11-16 | Genmab A/S | Traitement combine de tumeurs exprimant la cd38 |
| US20100173794A1 (en) | 2006-10-17 | 2010-07-08 | Koninklijke Philips Electronics N.V. | Device for amplification and detection of nucleic acids |
| EP1914242A1 (fr) | 2006-10-19 | 2008-04-23 | Sanofi-Aventis | Nouveau anticorps Anti-CD38 pour le traitement du cancer |
| US20100124583A1 (en) | 2008-04-30 | 2010-05-20 | Xyleco, Inc. | Processing biomass |
| GB0621973D0 (en) | 2006-11-03 | 2006-12-13 | Philogen Spa | Binding molecules and uses thereof |
| US20100112077A1 (en) | 2006-11-06 | 2010-05-06 | Abraxis Bioscience, Llc | Nanoparticles of paclitaxel and albumin in combination with bevacizumab against cancer |
| CN101578040A (zh) | 2006-11-07 | 2009-11-11 | 陶氏益农公司 | 可喷洒的、控制释放的灭雄技术(mat)制剂和昆虫防治方法 |
| US20110262525A1 (en) | 2006-12-13 | 2011-10-27 | Schering Corporation | Methods of treatment |
| CN104586815A (zh) | 2006-12-14 | 2015-05-06 | 阿布拉科斯生物科学有限公司 | 用包含紫杉烷的纳米颗粒基于激素受体状态治疗乳腺癌 |
| EP3417859A1 (fr) | 2007-03-07 | 2018-12-26 | Abraxis BioScience, LLC | Nanoparticule comprenant de la rapamycine et de l'albumine en tant qu'agent anti-cancéreux |
| AU2008224929A1 (en) | 2007-03-14 | 2008-09-18 | Mayo Foundation For Medical Education And Research | Treating skin cancer |
| WO2009005673A1 (fr) | 2007-06-28 | 2009-01-08 | Schering Corporation | Anti-igf1r |
| WO2009043159A1 (fr) | 2007-10-01 | 2009-04-09 | The Hospital For Sick Children | Cellules souches tumorales neurales et leurs procédés d'utilisation |
| EP2212432A4 (fr) | 2007-10-22 | 2011-10-19 | Schering Corp | Anticorps anti-vegf entièrement humains et leurs procédés d'utilisation |
| US8034905B2 (en) | 2007-11-09 | 2011-10-11 | Affitech Research, AS | Anti-VEGF antibody compositions and methods |
| DE102008013565A1 (de) | 2008-03-11 | 2009-09-17 | A. Kayser Automotive Systems Gmbh | Einsteckkupplung |
| EP3266453A1 (fr) | 2008-07-03 | 2018-01-10 | Mayo Foundation for Medical Education and Research | Traitement du cancer |
| US20100028416A1 (en) | 2008-07-30 | 2010-02-04 | Nitto Denko Corporation | Drug carriers |
| WO2010014784A2 (fr) | 2008-08-01 | 2010-02-04 | Bristol-Myers Squibb Company | Combinaison d'anticorps anti-ctla4 avec divers régimes thérapeutiques pour un traitement synergétique de maladies prolifératives |
| EP2321408A4 (fr) | 2008-08-04 | 2013-04-17 | Allocure Inc | Populations de cellules stromales mésenchymateuses et procédés d isolement et d utilisation de celles-ci |
| US8753604B2 (en) | 2008-12-23 | 2014-06-17 | Sanford-Burnham Medical Research Institute | Methods and compositions for synaphically-targeted treatment for cancer |
| BRPI1006141B8 (pt) | 2009-01-12 | 2021-05-25 | Cytomx Therapeutics Llc | composições de anticorpo modificado, métodos para preparar e usar as mesmas |
| JP5866117B2 (ja) | 2009-04-06 | 2016-02-17 | メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ | 分子を送達するための方法および材料 |
| US8571805B2 (en) | 2009-04-10 | 2013-10-29 | Pharmaco-Kinesis Corporation | Method and apparatus for detecting and regulating vascular endothelial growth factor (VEGF) by forming a homeostatic loop employing a half-antibody biosensor |
| BRPI1014160A2 (pt) | 2009-04-10 | 2015-08-25 | Abraxis Bioscience Llc | Formulações de nanopartículas e aplicações das mesmas |
| WO2010124009A2 (fr) | 2009-04-21 | 2010-10-28 | Schering Corporation | Anticorps anti-vegf entièrement humains et méthodes d'utilisation de ceux-ci |
| MX2011012691A (es) | 2009-05-28 | 2012-04-19 | Glaxo Group Ltd | Combinacion de un antagonista de tnf-alfa y un antagonista de vegf para utilizarse en el tratamiento o en la prevencion de enfermedades de los ojos. |
| AR078161A1 (es) | 2009-09-11 | 2011-10-19 | Hoffmann La Roche | Formulaciones farmaceuticas muy concentradas de un anticuerpo anti cd20. uso de la formulacion. metodo de tratamiento. |
| EP2496606A2 (fr) | 2009-11-05 | 2012-09-12 | The UAB Research Foundation | Traitement de cancers à génotype de type basal |
| KR20120106952A (ko) | 2009-11-13 | 2012-09-27 | 메르크 파텐트 게엠베하 | 화학요법제가 로딩된 나노입자와 연결된 항 인테그린 항체 |
| SG185798A1 (en) | 2010-06-07 | 2013-01-30 | Abraxis Bioscience Llc | Combination therapy methods for treating proliferative diseases |
| US20130281376A1 (en) | 2010-10-08 | 2013-10-24 | Abraxis Bioscience, Llc | Sparc microenvironment signature, plasma sparc, and ldh as prognostic biomarkers in the treatment of cancer |
| US20130281377A1 (en) | 2010-12-23 | 2013-10-24 | Mayo Foundation For Medical Education And Research | Treating multiple myeloma |
| US20120283290A1 (en) | 2011-05-06 | 2012-11-08 | Amicus Therapeutics Inc. | Quantitation of gl3 in urine |
| PT2707030T (pt) | 2011-05-09 | 2020-05-22 | Mayo Found Medical Education & Res | Tratamentos de cancro |
| US20130028895A1 (en) | 2011-07-27 | 2013-01-31 | Gerald Wulf | Exosome inhibiting agents and uses thereof |
| WO2013043569A1 (fr) | 2011-09-20 | 2013-03-28 | Vical Incorporated | Immunothérapie combinée à action antitumorale synergique faisant appel à des alloantigènes |
| WO2013071058A1 (fr) | 2011-11-09 | 2013-05-16 | The Uab Research Foundation | Anticorps her3 et utilisations de ceux-ci |
| US9856320B2 (en) * | 2012-05-15 | 2018-01-02 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting PD-1/PD-L1 signaling |
| PL2872157T3 (pl) | 2012-07-12 | 2020-07-13 | Hangzhou Dac Biotech Co., Ltd | Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi |
| WO2014037422A1 (fr) | 2012-09-04 | 2014-03-13 | Inven2 As | Expansion sélective et régulée de cellules nk éduquées |
| CA2917407C (fr) | 2012-10-01 | 2023-03-14 | Mayo Foundation For Medical Education And Research | Complexes de nanoparticules d'anticorps-albumine pour le traitement du cancer |
| US10342869B2 (en) | 2012-12-07 | 2019-07-09 | The Regents Of The University Of California | Compositions comprising anti-CD38 antibodies and lenalidomide |
| US20140186447A1 (en) | 2012-12-28 | 2014-07-03 | Abraxis Bioscience, Llc | Nanoparticle compositions of albumin and paclitaxel |
| CN105120859B (zh) | 2013-02-11 | 2018-10-09 | 阿布拉科斯生物科学有限公司 | 治疗黑素瘤的方法 |
| JP6942465B2 (ja) | 2013-09-27 | 2021-09-29 | ジェネンテック， インコーポレイテッド | 抗ｐｄｌ１抗体製剤 |
| JP2017507900A (ja) | 2013-12-17 | 2017-03-23 | ジェネンテック， インコーポレイテッド | Ｐｄ−１軸結合アンタゴニスト及び抗ｈｅｒ２抗体を使用してｈｅｒ２陽性がんを治療する方法 |
| KR102450563B1 (ko) | 2014-06-13 | 2022-10-07 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | 림프종의 치료 |
| US10213513B2 (en) | 2014-06-16 | 2019-02-26 | Mayo Foundation For Medical Education And Research | Treating myelomas |
| US9446148B2 (en) | 2014-10-06 | 2016-09-20 | Mayo Foundation For Medical Education And Research | Carrier-antibody compositions and methods of making and using the same |
| SI3204413T1 (sl) | 2014-10-06 | 2020-07-31 | Mayo Foundation For Medical Education And Research | Sestave protiteles prenašalca ter metode za njihovo izdelavo in uporabo |
| WO2016059220A1 (fr) | 2014-10-16 | 2016-04-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Agents d'activation du tcr à utiliser dans le traitement de la lla-t |
| JP2018501218A (ja) * | 2014-12-02 | 2018-01-18 | セルジーン コーポレイション | 併用療法 |
| CA2995384A1 (fr) | 2015-08-18 | 2017-02-23 | Mayo Foundation For Medical Education And Research | Compositions de support-agent de liaison et leurs procedes de fabrication et d'utilisation |
| TW201707725A (zh) | 2015-08-18 | 2017-03-01 | 美國馬友醫藥教育研究基金會 | 載體－抗體組合物及其製造及使用方法 |
| WO2017176265A1 (fr) | 2016-04-06 | 2017-10-12 | Mayo Foundation For Medical Education And Research | Compositions de support-agent de liaison et leurs procédés de fabrication et d'utilisation |
| TW201713360A (en) | 2015-10-06 | 2017-04-16 | Mayo Foundation | Methods of treating cancer using compositions of antibodies and carrier proteins |
| EP3399861A4 (fr) | 2016-01-07 | 2019-08-07 | Mayo Foundation for Medical Education and Research | Procédés de traitement du cancer par interféron |
| CN109072817A (zh) | 2016-01-08 | 2018-12-21 | 创科（澳门离岸商业服务）有限公司 | 具有维护端口的化油器 |
| EP3413874A4 (fr) | 2016-02-12 | 2020-01-22 | Mayo Foundation for Medical Education and Research | Traitements des cancers hématologiques |
| AU2017238118A1 (en) | 2016-03-21 | 2018-10-11 | Mayo Foundation For Medical Education And Research | Methods for improving the therapeutic index for a chemotherapeutic drug |
| US11305020B2 (en) | 2016-03-21 | 2022-04-19 | Mayo Foundation For Medical Education And Research | Methods for reducing toxicity of a chemotherapeutic drug |
| US10618969B2 (en) | 2016-04-06 | 2020-04-14 | Mayo Foundation For Medical Education And Research | Carrier-binding agent compositions and methods of making and using the same |
| CA3032947A1 (fr) | 2016-08-05 | 2018-02-08 | Mayo Foundation For Medical Education And Research | Complexes de nanoparticules d'anticorps-albumine modifiees pour le traitement du cancer. |
| RU2019109209A (ru) | 2016-09-01 | 2020-10-05 | Мэйо Фаундейшн Фор Медикал Эдьюкейшн Энд Рисерч | Способ и композиции для направленного на мишень воздействия при лечении т-клеточных видов рака |
| KR20220151022A (ko) | 2016-09-01 | 2022-11-11 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | 암 치료용 담체－ｐｄ－ｌ１ 결합제 조성물 |
| KR20230011473A (ko) | 2016-09-06 | 2023-01-20 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | Ｐｄ－ｌ１ 발현 암의 치료 방법 |
| US11311631B2 (en) | 2016-09-06 | 2022-04-26 | Mayo Foundation For Medical Education And Research | Paclitaxel-albumin-binding agent compositions and methods for using and making the same |
| US11590098B2 (en) | 2016-09-06 | 2023-02-28 | Mayo Foundation For Medical Education And Research | Methods of treating triple-negative breast cancer using compositions of antibodies and carrier proteins |
| EP3533870A4 (fr) | 2016-10-28 | 2020-04-08 | NRL Pharma, Inc. | Protéine de fusion lactoferrine/albumine et son procédé de production |
-
2017
- 2017-08-31 KR KR1020227037674A patent/KR20220151022A/ko not_active Application Discontinuation
- 2017-08-31 ES ES17778387T patent/ES2937291T3/es active Active
- 2017-08-31 AU AU2017318668A patent/AU2017318668A1/en not_active Withdrawn
- 2017-08-31 EP EP17778387.5A patent/EP3506942B1/fr active Active
- 2017-08-31 CN CN201780067542.2A patent/CN109890419A/zh active Pending
- 2017-08-31 CA CA3035378A patent/CA3035378A1/fr active Pending
- 2017-08-31 US US16/330,030 patent/US11548946B2/en active Active
- 2017-08-31 MX MX2019002474A patent/MX2019002474A/es unknown
- 2017-08-31 WO PCT/US2017/049746 patent/WO2018045239A1/fr unknown
- 2017-08-31 EP EP22206923.9A patent/EP4177271A1/fr active Pending
- 2017-08-31 RU RU2019109211A patent/RU2019109211A/ru not_active Application Discontinuation
- 2017-08-31 KR KR1020197009302A patent/KR102462041B1/ko active IP Right Grant
- 2017-08-31 JP JP2019511962A patent/JP2019526578A/ja active Pending
-
2022
- 2022-04-11 JP JP2022065086A patent/JP2022082806A/ja active Pending
- 2022-11-18 US US18/057,165 patent/US20230159640A1/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| KRISTA ROSA: "Atezolizumab/Chemotherapy Combo Misses PFS Endpoint in Frontline PD-L1 + TNBC", ONCLIVE, 7 August 2020 (2020-08-07) * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP4177271A1 (fr) | 2023-05-10 |
| KR20190129818A (ko) | 2019-11-20 |
| AU2017318668A1 (en) | 2019-03-21 |
| RU2019109211A (ru) | 2020-10-01 |
| ES2937291T3 (es) | 2023-03-27 |
| MX2019002474A (es) | 2019-09-18 |
| CN109890419A (zh) | 2019-06-14 |
| KR102462041B1 (ko) | 2022-11-02 |
| US11548946B2 (en) | 2023-01-10 |
| US20230159640A1 (en) | 2023-05-25 |
| JP2019526578A (ja) | 2019-09-19 |
| WO2018045239A1 (fr) | 2018-03-08 |
| EP3506942A1 (fr) | 2019-07-10 |
| US20190202916A1 (en) | 2019-07-04 |
| KR20220151022A (ko) | 2022-11-11 |
| CA3035378A1 (fr) | 2018-03-08 |
| JP2022082806A (ja) | 2022-06-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3506942B1 (fr) | Compositions d'agents de liaison et de porteuses pd-l1 pour le traitement de cancers | |
| JP7477469B2 (ja) | 担体および抗体からなる組成物およびその製造および使用方法 | |
| JP7025412B2 (ja) | パクリタキセル－アルブミン－結合剤組成物並びに該組成物の使用及び製造方法 | |
| JP7133050B2 (ja) | キャリア結合剤組成物およびそれを作製および使用する方法 | |
| US20210402005A1 (en) | Methods and compositions for targeting t-cell cancers | |
| EP4208204A1 (fr) | Complexes anticorps-nanoparticules et leurs procédés de fabrication et méthodes d'utilisation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: UNKNOWN |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE |
|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE |
|
| 17P | Request for examination filed |
Effective date: 20190319 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
| AX | Request for extension of the european patent |
Extension state: BA ME |
|
| DAV | Request for validation of the european patent (deleted) | ||
| DAX | Request for extension of the european patent (deleted) | ||
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: EXAMINATION IS IN PROGRESS |
|
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40004904 Country of ref document: HK |
|
| 17Q | First examination report despatched |
Effective date: 20200416 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: EXAMINATION IS IN PROGRESS |
|
| GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: GRANT OF PATENT IS INTENDED |
|
| INTG | Intention to grant announced |
Effective date: 20220301 |
|
| GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE PATENT HAS BEEN GRANTED |
|
| AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
| REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
| REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 602017063773 Country of ref document: DE |
|
| REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 1531362 Country of ref document: AT Kind code of ref document: T Effective date: 20221215 |
|
| REG | Reference to a national code |
Ref country code: NL Ref legal event code: FP |
|
| REG | Reference to a national code |
Ref country code: LT Ref legal event code: MG9D |
|
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2937291 Country of ref document: ES Kind code of ref document: T3 Effective date: 20230327 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: PT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230316 Ref country code: NO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230216 Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: RS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: PL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: LV Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230316 Ref country code: HR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230217 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SM Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 |
|
| REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 602017063773 Country of ref document: DE |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 Ref country code: AL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 |
|
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 20230826 Year of fee payment: 7 |
|
| 26N | No opposition filed |
Effective date: 20230817 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20230822 Year of fee payment: 7 Ref country code: GB Payment date: 20230828 Year of fee payment: 7 Ref country code: ES Payment date: 20230901 Year of fee payment: 7 Ref country code: CH Payment date: 20230903 Year of fee payment: 7 Ref country code: AT Payment date: 20230802 Year of fee payment: 7 |
|
| REG | Reference to a national code |
Ref country code: AT Ref legal event code: UEP Ref document number: 1531362 Country of ref document: AT Kind code of ref document: T Effective date: 20221116 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20230825 Year of fee payment: 7 Ref country code: BE Payment date: 20230828 Year of fee payment: 7 |
|
| REG | Reference to a national code |
Ref country code: DE Ref legal event code: R119 Ref document number: 602017063773 Country of ref document: DE |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20221116 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20230831 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20230831 |